期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：12
页码：E1490-E1497
DOI：10.1073/pnas.1410400112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe search for new antifungal compounds is struggling to keep pace with emerging fungicide resistance. Through chemoprospecting of an untapped reservoir of inhibitory compounds, lignocellulosic hydrolysates, we have identified a previously undescribed antifungal agent, poacic acid. Using both chemical genomics and morphological analysis together for the first time, to our knowledge, we identified the cellular target of poacic acid as {beta}-1,3-glucan. Through its action on the glucan layer of fungal cell walls, poacic acid is a natural antifungal agent against economically significant fungi and oomycete plant pathogens. This work highlights the chemical diversity within lignocellulosic hydrolysates as a source of potentially valuable chemicals. A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited {beta}-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding {beta}-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting {beta}-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates.
